MCID: NTR007
MIFTS: 36

Neutral Lipid Storage Disease with Myopathy

Categories: Genetic diseases, Rare diseases, Neuronal diseases, Metabolic diseases, Cardiovascular diseases

Aliases & Classifications for Neutral Lipid Storage Disease with Myopathy

MalaCards integrated aliases for Neutral Lipid Storage Disease with Myopathy:

Name: Neutral Lipid Storage Disease with Myopathy 57 53 25 75 37 29 13 6 73
Nlsdm 57 53 25 59 75
Neutral Lipid Storage Disease Without Ichthyosis 57 53 25 75
Neutral Lipid Storage Disease with Myopathy Without Ichthyosis 59
Lipid, Neutral, Storage Disease with Myopathy 40
Triglyceride Storage Disease with Ichthyosis 73
Triglyceride Deposit Cardiomyovasculopathy 59
Neutral Lipid Storage Myopathy 59

Characteristics:

Orphanet epidemiological data:

59
neutral lipid storage myopathy
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Adult;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
adult onset
variable severity
slowly progressive
cardiomyopathy may develop later in the disease
heterozygous mutation carriers may show mild symptoms


HPO:

32
neutral lipid storage disease with myopathy:
Onset and clinical course variable expressivity adult onset slow progression
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Neutral Lipid Storage Disease with Myopathy

OMIM : 57 Neutral lipid storage disease with myopathy is an autosomal recessive muscle disorder characterized by adult onset of slowly progressive proximal muscle weakness affecting the upper and lower limbs and associated with increased serum creatine kinase; distal muscle weakness may also occur. About half of patients develop cardiomyopathy later in the disease course. Other variable features include diabetes mellitus, hepatic steatosis, hypertriglyceridemia, and possibly sensorineural hearing loss. Leukocytes and muscle cells show cytoplasmic accumulation of triglycerides (summary by Reilich et al., 2011). Neutral lipid storage disease with myopathy belongs to a group of disorders termed neutral lipid storage disorders (NLSDs). These disorders are characterized by the presence of triglyceride-containing cytoplasmic droplets in leukocytes and in other tissues, including bone marrow, skin, and muscle. Chanarin-Dorfman syndrome (CDS; 275630) is defined as NLSD with ichthyosis (NLSDI). Patients with NLSDM present with myopathy but without ichthyosis (summary by Fischer et al., 2007). (610717)

MalaCards based summary : Neutral Lipid Storage Disease with Myopathy, also known as nlsdm, is related to lipid storage disease and lipidosis with triglycerid storage disease, and has symptoms including ataxia, muscle weakness and muscular fasciculation. An important gene associated with Neutral Lipid Storage Disease with Myopathy is PNPLA2 (Patatin Like Phospholipase Domain Containing 2), and among its related pathways/superpathways is Regulation of lipolysis in adipocytes. The drugs Bezafibrate and Anticholesteremic Agents have been mentioned in the context of this disorder. Affiliated tissues include liver, skin and bone, and related phenotypes are diabetes mellitus and hepatomegaly

Genetics Home Reference : 25 Neutral lipid storage disease with myopathy is a condition in which fats (lipids) are stored abnormally in organs and tissues throughout the body. People with this condition have muscle weakness (myopathy) due to the accumulation of fats in muscle tissue. Other features of this condition may include a fatty liver, a weakened and enlarged heart (cardiomyopathy), inflammation of the pancreas (pancreatitis), reduced thyroid activity (hypothyroidism), and type 2 diabetes (the most common form of diabetes). Signs and symptoms of neutral lipid storage disease with myopathy vary greatly among affected individuals.

NIH Rare Diseases : 53 Neutral lipid storage disease with myopathy is a condition in which fats (lipids) are stored abnormally in organs and tissues throughout the body. The accumulation of fats in muscle tissue leads to muscle weakness (myopathy). This condition is caused by mutations in the PNPLA2 gene. It is inherited in an autosomal recessive pattern. There is currently no treatment to correct the underlying metabolic problem.

UniProtKB/Swiss-Prot : 75 Neutral lipid storage disease with myopathy: Neutral lipid storage disorder (NLSD) with myopathy but without ichthyosis. NLSDs are characterized by the presence of triglyceride- containing cytoplasmic droplets in leukocytes and in other tissues, including bone marrow, skin, and muscle. Individuals with NLSDM did not show obesity, in spite of a defect in triglyceride degradation in fibroblasts and in marked triglyceride storage in liver, muscles, and other visceral cells.

Related Diseases for Neutral Lipid Storage Disease with Myopathy

Diseases related to Neutral Lipid Storage Disease with Myopathy via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 lipid storage disease 29.4 CRACR2B PNPLA2
2 lipidosis with triglycerid storage disease 11.2
3 myopathy 10.6

Symptoms & Phenotypes for Neutral Lipid Storage Disease with Myopathy

Symptoms via clinical synopsis from OMIM:

57
Muscle Soft Tissue:
myopathy
fasciculations
difficulty walking
easy fatigability
difficulty running
more
Growth Height:
short stature (in some patients)

Head And Neck Ears:
hearing loss, sensorineural (in some patients)

Cardiovascular Heart:
cardiomyopathy (in some patients)

Head And Neck Neck:
neck muscle weakness (in some patients)

Neurologic Central Nervous System:
delayed walking (rare)

Abdomen Liver:
hepatic steatosis
abnormal liver enzymes
hepatomegaly (in some patients)

Laboratory Abnormalities:
increased serum creatine kinase
abnormal liver enzymes
accumulation of neutral lipids (triglycerides) in leukocytes, muscle cells, fibroblasts, and cardiomyocytes
lipid vacuoles in leukocytes (jordan bodies)
increased serum triglycerides (in some patients)

Neurologic Peripheral Nervous System:
areflexia (in some patients)

Endocrine Features:
diabetes mellitus (in some patients)

Skin Nails Hair Skin:
no ichthyosis


Clinical features from OMIM:

610717

Human phenotypes related to Neutral Lipid Storage Disease with Myopathy:

32 (show all 22)
# Description HPO Frequency HPO Source Accession
1 diabetes mellitus 32 occasional (7.5%) HP:0000819
2 hepatomegaly 32 HP:0002240
3 sensorineural hearing impairment 32 occasional (7.5%) HP:0000407
4 short stature 32 occasional (7.5%) HP:0004322
5 myopathy 32 HP:0003198
6 elevated serum creatine phosphokinase 32 HP:0003236
7 hypertriglyceridemia 32 occasional (7.5%) HP:0002155
8 hepatic steatosis 32 HP:0001397
9 elevated hepatic transaminases 32 HP:0002910
10 cardiomyopathy 32 occasional (7.5%) HP:0001638
11 myalgia 32 HP:0003326
12 areflexia 32 occasional (7.5%) HP:0001284
13 fasciculations 32 HP:0002380
14 difficulty walking 32 HP:0002355
15 exercise intolerance 32 HP:0003546
16 neck muscle weakness 32 occasional (7.5%) HP:0000467
17 proximal muscle weakness 32 HP:0003701
18 generalized hypotonia 32 HP:0001290
19 increased muscle lipid content 32 HP:0009058
20 easy fatigability 32 HP:0003388
21 difficulty running 32 HP:0009046
22 gowers sign 32 HP:0003391

UMLS symptoms related to Neutral Lipid Storage Disease with Myopathy:


ataxia, muscle weakness, muscular fasciculation, myalgia

Drugs & Therapeutics for Neutral Lipid Storage Disease with Myopathy

Drugs for Neutral Lipid Storage Disease with Myopathy (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 6)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Bezafibrate Approved, Investigational Phase 4 41859-67-0 39042
2 Anticholesteremic Agents Phase 4
3 Antimetabolites Phase 4
4 Clofibric Acid Phase 4 882-09-7
5 Hypolipidemic Agents Phase 4
6 Lipid Regulating Agents Phase 4

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 The Effect of Fibrate Therapy in Two Patients With Neutral Lipid Storage Disease With Myopathy (NLSDM) Completed NCT01527318 Phase 4 Fibrate treatment
2 International Registry Study of Neutral Lipid Storage Disease (NLSD) / Triglyceride Deposit Cardiomyovasculopathy (TGCV) and Related Diseases Recruiting NCT02918032
3 Clinical Study on the Safety of CNT-02 for TGCV and NLSD-M Enrolling by invitation NCT02830763 Not Applicable

Search NIH Clinical Center for Neutral Lipid Storage Disease with Myopathy

Genetic Tests for Neutral Lipid Storage Disease with Myopathy

Genetic tests related to Neutral Lipid Storage Disease with Myopathy:

# Genetic test Affiliating Genes
1 Neutral Lipid Storage Disease with Myopathy 29 PNPLA2

Anatomical Context for Neutral Lipid Storage Disease with Myopathy

MalaCards organs/tissues related to Neutral Lipid Storage Disease with Myopathy:

41
Liver, Skin, Bone, Bone Marrow, Heart, Pancreas, Thyroid

Publications for Neutral Lipid Storage Disease with Myopathy

Articles related to Neutral Lipid Storage Disease with Myopathy:

(show all 15)
# Title Authors Year
1
Patients with neutral lipid storage disease with myopathy (NLSDM) in Southwestern China. ( 29539587 )
2018
2
Neutral lipid storage disease with myopathy: Further phenotypic characterization of a rare PNPLA2 variant. ( 29779757 )
2018
3
Neutral lipid-storage disease with myopathy and extended phenotype with novel PNPLA2 mutation. ( 26600210 )
2016
4
Novel missense mutations in PNPLA2 causing late onset and clinical heterogeneity of neutral lipid storage disease with myopathy in three siblings. ( 25956450 )
2015
5
Peripheral leukocyte anomaly detected with routine automated hematology analyzer sensitive to adipose triglyceride lipase deficiency manifesting neutral lipid storage disease with myopathy/triglyceride deposit cardiomyovasculopathy. ( 27896096 )
2014
6
A novel mutation in PNPLA2 causes neutral lipid storage disease with myopathy and triglyceride deposit cardiomyovasculopathy: a case report and literature review. ( 24836204 )
2014
7
Muscle mri in neutral lipid storage disease with myopathy carrying mutation c.187+1G&amp;gt;A. ( 25363365 )
2014
8
Metabolic consequences of adipose triglyceride lipase deficiency in humans: an in vivo study in patients with neutral lipid storage disease with myopathy. ( 23824421 )
2013
9
Effects of bezafibrate treatment in a patient and a carrier with mutations in the PNPLA2 gene, causing neutral lipid storage disease with myopathy. ( 23449549 )
2013
10
Neutral lipid storage disease with myopathy: a whole-body nuclear MRI and metabolic study. ( 23333026 )
2013
11
Novel PNPLA2 gene mutations in Chinese Han patients causing neutral lipid storage disease with myopathy. ( 22832386 )
2012
12
A novel mutation in PNPLA2 leading to neutral lipid storage disease with myopathy. ( 22964912 )
2012
13
A novel PNPLA2 mutation causes neutral lipid storage disease with myopathy (NLSDM) presenting muscular dystrophic features with lipid storage and rimmed vacuoles. ( 21073837 )
2010
14
Novel mutations in the adipose triglyceride lipase gene causing neutral lipid storage disease with myopathy. ( 18952067 )
2008
15
The gene encoding adipose triglyceride lipase (PNPLA2) is mutated in neutral lipid storage disease with myopathy. ( 17187067 )
2007

Variations for Neutral Lipid Storage Disease with Myopathy

UniProtKB/Swiss-Prot genetic disease variations for Neutral Lipid Storage Disease with Myopathy:

75
# Symbol AA change Variation ID SNP ID
1 PNPLA2 p.Pro195Leu VAR_032995 rs121918259

ClinVar genetic disease variations for Neutral Lipid Storage Disease with Myopathy:

6
(show top 50) (show all 190)
# Gene Variation Type Significance SNP ID Assembly Location
1 PNPLA2 NM_020376.3(PNPLA2): c.808delC (p.His270Thrfs) deletion Pathogenic rs796065303 GRCh37 Chromosome 11, 823744: 823744
2 PNPLA2 NM_020376.3(PNPLA2): c.808delC (p.His270Thrfs) deletion Pathogenic rs796065303 GRCh38 Chromosome 11, 823744: 823744
3 PNPLA2 NM_020376.3(PNPLA2): c.584C> T (p.Pro195Leu) single nucleotide variant Pathogenic rs121918259 GRCh37 Chromosome 11, 822494: 822494
4 PNPLA2 NM_020376.3(PNPLA2): c.584C> T (p.Pro195Leu) single nucleotide variant Pathogenic rs121918259 GRCh38 Chromosome 11, 822494: 822494
5 PNPLA2 NM_020376.3(PNPLA2): c.847delC (p.Gln283Lysfs) deletion Pathogenic rs796065304 GRCh37 Chromosome 11, 823783: 823783
6 PNPLA2 NM_020376.3(PNPLA2): c.847delC (p.Gln283Lysfs) deletion Pathogenic rs796065304 GRCh38 Chromosome 11, 823783: 823783
7 PNPLA2 NM_020376.3(PNPLA2): c.865C> T (p.Gln289Ter) single nucleotide variant Pathogenic rs121918260 GRCh37 Chromosome 11, 823801: 823801
8 PNPLA2 NM_020376.3(PNPLA2): c.865C> T (p.Gln289Ter) single nucleotide variant Pathogenic rs121918260 GRCh38 Chromosome 11, 823801: 823801
9 PNPLA2 NM_020376.3(PNPLA2): c.757+2T> C single nucleotide variant Pathogenic rs777539013 GRCh37 Chromosome 11, 823589: 823589
10 PNPLA2 NM_020376.3(PNPLA2): c.757+2T> C single nucleotide variant Pathogenic rs777539013 GRCh38 Chromosome 11, 823589: 823589
11 PNPLA2 NM_020376.3(PNPLA2): c.749A> C (p.Gln250Pro) single nucleotide variant Pathogenic rs397514625 GRCh37 Chromosome 11, 823579: 823579
12 PNPLA2 NM_020376.3(PNPLA2): c.749A> C (p.Gln250Pro) single nucleotide variant Pathogenic rs397514625 GRCh38 Chromosome 11, 823579: 823579
13 PNPLA2 NM_020376.3(PNPLA2): c.757+1G> T single nucleotide variant Pathogenic rs869320738 GRCh37 Chromosome 11, 823588: 823588
14 PNPLA2 NM_020376.3(PNPLA2): c.757+1G> T single nucleotide variant Pathogenic rs869320738 GRCh38 Chromosome 11, 823588: 823588
15 PNPLA2 NM_020376.3(PNPLA2): c.467delC (p.Pro156Leufs) deletion Pathogenic rs796065307 GRCh37 Chromosome 11, 822004: 822004
16 PNPLA2 NM_020376.3(PNPLA2): c.467delC (p.Pro156Leufs) deletion Pathogenic rs796065307 GRCh38 Chromosome 11, 822004: 822004
17 PNPLA2 NM_020376.3(PNPLA2): c.613dupC (p.Leu205Profs) duplication Pathogenic rs796065308 GRCh37 Chromosome 11, 822523: 822523
18 PNPLA2 NM_020376.3(PNPLA2): c.613dupC (p.Leu205Profs) duplication Pathogenic rs796065308 GRCh38 Chromosome 11, 822523: 822523
19 PNPLA2 NM_020376.3(PNPLA2): c.543delC (p.Ile182Serfs) deletion Pathogenic rs796065309 GRCh37 Chromosome 11, 822453: 822453
20 PNPLA2 NM_020376.3(PNPLA2): c.543delC (p.Ile182Serfs) deletion Pathogenic rs796065309 GRCh38 Chromosome 11, 822453: 822453
21 PNPLA2 NM_020376.3(PNPLA2): c.475_478dupCTCC (p.Gln160Profs) duplication Pathogenic rs796065310 GRCh38 Chromosome 11, 822012: 822015
22 PNPLA2 NM_020376.3(PNPLA2): c.475_478dupCTCC (p.Gln160Profs) duplication Pathogenic rs796065310 GRCh37 Chromosome 11, 822012: 822015
23 PNPLA2 NM_020376.3(PNPLA2): c.793C> T (p.Pro265Ser) single nucleotide variant Benign/Likely benign rs56152088 GRCh37 Chromosome 11, 823729: 823729
24 PNPLA2 NM_020376.3(PNPLA2): c.793C> T (p.Pro265Ser) single nucleotide variant Benign/Likely benign rs56152088 GRCh38 Chromosome 11, 823729: 823729
25 PNPLA2 NM_020376.3(PNPLA2): c.187+15G> A single nucleotide variant Likely benign rs371958663 GRCh37 Chromosome 11, 819920: 819920
26 PNPLA2 NM_020376.3(PNPLA2): c.187+15G> A single nucleotide variant Likely benign rs371958663 GRCh38 Chromosome 11, 819920: 819920
27 PNPLA2 NM_020376.3(PNPLA2): c.246C> A (p.Gly82=) single nucleotide variant Benign rs200701730 GRCh37 Chromosome 11, 821686: 821686
28 PNPLA2 NM_020376.3(PNPLA2): c.246C> A (p.Gly82=) single nucleotide variant Benign rs200701730 GRCh38 Chromosome 11, 821686: 821686
29 PNPLA2 NM_020376.3(PNPLA2): c.369C> T (p.Asp123=) single nucleotide variant Conflicting interpretations of pathogenicity rs142174851 GRCh38 Chromosome 11, 821809: 821809
30 PNPLA2 NM_020376.3(PNPLA2): c.369C> T (p.Asp123=) single nucleotide variant Conflicting interpretations of pathogenicity rs142174851 GRCh37 Chromosome 11, 821809: 821809
31 PNPLA2 NM_020376.3(PNPLA2): c.487-8C> T single nucleotide variant Conflicting interpretations of pathogenicity rs201418203 GRCh37 Chromosome 11, 822389: 822389
32 PNPLA2 NM_020376.3(PNPLA2): c.487-8C> T single nucleotide variant Conflicting interpretations of pathogenicity rs201418203 GRCh38 Chromosome 11, 822389: 822389
33 PNPLA2 NM_020376.3(PNPLA2): c.678C> T (p.Leu226=) single nucleotide variant Benign/Likely benign rs10902224 GRCh37 Chromosome 11, 822588: 822588
34 PNPLA2 NM_020376.3(PNPLA2): c.678C> T (p.Leu226=) single nucleotide variant Benign/Likely benign rs10902224 GRCh38 Chromosome 11, 822588: 822588
35 PNPLA2 NM_020376.3(PNPLA2): c.756C> G (p.Asn252Lys) single nucleotide variant Benign rs140201358 GRCh37 Chromosome 11, 823586: 823586
36 PNPLA2 NM_020376.3(PNPLA2): c.756C> G (p.Asn252Lys) single nucleotide variant Benign rs140201358 GRCh38 Chromosome 11, 823586: 823586
37 PNPLA2 NM_020376.3(PNPLA2): c.873C> G (p.Pro291=) single nucleotide variant Benign rs1135628 GRCh37 Chromosome 11, 823809: 823809
38 PNPLA2 NM_020376.3(PNPLA2): c.873C> G (p.Pro291=) single nucleotide variant Benign rs1135628 GRCh38 Chromosome 11, 823809: 823809
39 PNPLA2 NM_020376.3(PNPLA2): c.919+4C> T single nucleotide variant Benign/Likely benign rs148314086 GRCh37 Chromosome 11, 823859: 823859
40 PNPLA2 NM_020376.3(PNPLA2): c.919+4C> T single nucleotide variant Benign/Likely benign rs148314086 GRCh38 Chromosome 11, 823859: 823859
41 PNPLA2 NM_020376.3(PNPLA2): c.1149G> A (p.Arg383=) single nucleotide variant Benign/Likely benign rs150770244 GRCh37 Chromosome 11, 824410: 824410
42 PNPLA2 NM_020376.3(PNPLA2): c.1149G> A (p.Arg383=) single nucleotide variant Benign/Likely benign rs150770244 GRCh38 Chromosome 11, 824410: 824410
43 PNPLA2 NM_020376.3(PNPLA2): c.1167G> T (p.Leu389=) single nucleotide variant Benign rs11554663 GRCh37 Chromosome 11, 824428: 824428
44 PNPLA2 NM_020376.3(PNPLA2): c.1167G> T (p.Leu389=) single nucleotide variant Benign rs11554663 GRCh38 Chromosome 11, 824428: 824428
45 PNPLA2 NM_020376.3(PNPLA2): c.1327C> G (p.Leu443Val) single nucleotide variant Conflicting interpretations of pathogenicity rs182948893 GRCh37 Chromosome 11, 824674: 824674
46 PNPLA2 NM_020376.3(PNPLA2): c.1327C> G (p.Leu443Val) single nucleotide variant Conflicting interpretations of pathogenicity rs182948893 GRCh38 Chromosome 11, 824674: 824674
47 PNPLA2 NM_020376.3(PNPLA2): c.1364C> A (p.Pro455Gln) single nucleotide variant Conflicting interpretations of pathogenicity rs187668158 GRCh37 Chromosome 11, 824711: 824711
48 PNPLA2 NM_020376.3(PNPLA2): c.1364C> A (p.Pro455Gln) single nucleotide variant Conflicting interpretations of pathogenicity rs187668158 GRCh38 Chromosome 11, 824711: 824711
49 PNPLA2 NM_020376.3(PNPLA2): c.1430C> G (p.Pro477Arg) single nucleotide variant Benign/Likely benign rs142588621 GRCh38 Chromosome 11, 824777: 824777
50 PNPLA2 NM_020376.3(PNPLA2): c.1430C> G (p.Pro477Arg) single nucleotide variant Benign/Likely benign rs142588621 GRCh37 Chromosome 11, 824777: 824777

Expression for Neutral Lipid Storage Disease with Myopathy

Search GEO for disease gene expression data for Neutral Lipid Storage Disease with Myopathy.

Pathways for Neutral Lipid Storage Disease with Myopathy

Pathways related to Neutral Lipid Storage Disease with Myopathy according to KEGG:

37
# Name Kegg Source Accession
1 Regulation of lipolysis in adipocytes hsa04923

GO Terms for Neutral Lipid Storage Disease with Myopathy

Sources for Neutral Lipid Storage Disease with Myopathy

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
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32 HPO
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34 ICD10 via Orphanet
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37 KEGG
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40 LOVD
42 MedGen
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45 MESH via Orphanet
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58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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